Abstract
The whirler mouse mutant (wi) does not respond to sound stimuli, and detailed ultrastructural analysis of sensory hair cells in the organ of Corti of the inner ear indicates that the whirler gene encodes a protein involved in the elongation and maintenance of stereocilia in both inner hair cells (IHCs) and outer hair cells (OHCs). BAC-mediated transgene correction of the mouse phenotype and mutation analysis identified the causative gene as encoding a novel PDZ protein called whirlin. The gene encoding whirlin also underlies the human autosomal recessive deafness locus DFNB31. In the mouse cochlea, whirlin is expressed in the sensory IHC and OHC stereocilia. Our findings suggest that this novel PDZ domain-containing molecule acts as an organizer of submembranous molecular complexes that control the coordinated actin polymerization and membrane growth of stereocilia.
| Original language | English |
|---|---|
| Pages (from-to) | 421-428 |
| Number of pages | 8 |
| Journal | Nature Genetics |
| Volume | 34 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 1 2003 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31. / Mburu, Philomena; Mustapha, Mirna; Varela, Anabel; Weil, Dominique; El-Amraoui, Aziz; Holme, Ralph H.; Rump, Andreas; Hardisty, Rachel E.; Blanchard, Stéphane; Coimbra, Roney S.; Perfettini, Isabelle; Parkinson, Nick; Mallon, Ann Marie; Glenister, Pete; Rogers, Mike J.; Paige, Adam J.; Moir, Lee; Clay, Jo; Rosenthal, Andre; Liu, Xue Z; Blanco, Gonzalo; Steel, Karen P.; Petit, Christine; Brown, Steve D M.
In: Nature Genetics, Vol. 34, No. 4, 01.08.2003, p. 421-428.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31
AU - Mburu, Philomena
AU - Mustapha, Mirna
AU - Varela, Anabel
AU - Weil, Dominique
AU - El-Amraoui, Aziz
AU - Holme, Ralph H.
AU - Rump, Andreas
AU - Hardisty, Rachel E.
AU - Blanchard, Stéphane
AU - Coimbra, Roney S.
AU - Perfettini, Isabelle
AU - Parkinson, Nick
AU - Mallon, Ann Marie
AU - Glenister, Pete
AU - Rogers, Mike J.
AU - Paige, Adam J.
AU - Moir, Lee
AU - Clay, Jo
AU - Rosenthal, Andre
AU - Liu, Xue Z
AU - Blanco, Gonzalo
AU - Steel, Karen P.
AU - Petit, Christine
AU - Brown, Steve D M
PY - 2003/8/1
Y1 - 2003/8/1
N2 - The whirler mouse mutant (wi) does not respond to sound stimuli, and detailed ultrastructural analysis of sensory hair cells in the organ of Corti of the inner ear indicates that the whirler gene encodes a protein involved in the elongation and maintenance of stereocilia in both inner hair cells (IHCs) and outer hair cells (OHCs). BAC-mediated transgene correction of the mouse phenotype and mutation analysis identified the causative gene as encoding a novel PDZ protein called whirlin. The gene encoding whirlin also underlies the human autosomal recessive deafness locus DFNB31. In the mouse cochlea, whirlin is expressed in the sensory IHC and OHC stereocilia. Our findings suggest that this novel PDZ domain-containing molecule acts as an organizer of submembranous molecular complexes that control the coordinated actin polymerization and membrane growth of stereocilia.
AB - The whirler mouse mutant (wi) does not respond to sound stimuli, and detailed ultrastructural analysis of sensory hair cells in the organ of Corti of the inner ear indicates that the whirler gene encodes a protein involved in the elongation and maintenance of stereocilia in both inner hair cells (IHCs) and outer hair cells (OHCs). BAC-mediated transgene correction of the mouse phenotype and mutation analysis identified the causative gene as encoding a novel PDZ protein called whirlin. The gene encoding whirlin also underlies the human autosomal recessive deafness locus DFNB31. In the mouse cochlea, whirlin is expressed in the sensory IHC and OHC stereocilia. Our findings suggest that this novel PDZ domain-containing molecule acts as an organizer of submembranous molecular complexes that control the coordinated actin polymerization and membrane growth of stereocilia.
UR - http://www.scopus.com/inward/record.url?scp=0043168114&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0043168114&partnerID=8YFLogxK
U2 - 10.1038/ng1208
DO - 10.1038/ng1208
M3 - Article
C2 - 12833159
AN - SCOPUS:0043168114
VL - 34
SP - 421
EP - 428
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 4
ER -